ANTI-PROLIFERATIVE EFFECT OF HISTONE DEACETYLASE INHIBITORS ON MURINE EMBRYONIC STEM CELLS
I. A. Chuykin,1 M. S. Lianguzova, V. A. Pospelov
Institute of Cytology RAS, St. Petersburg;
1 e-mail: chuykin79@mail.ru
The effect of histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butirate (NaBut) on the
proliferation of murine embryonic stem cells (MESC) was studied. Both agents suppressed the population growth and
clonability of MESC. Flow cytometry analysis showed a decrease in the amount of S-phase cells upon treatment with
HDAC inhibitors. TSA treatment caused a decrease in mRNA level of such positive cell cycle regulators as cyclins
D1, A, ñ-myc, cdc25A, and induced transcription of negative regulators of the cell cycle -
p21Waf1 and p57kip2. Also, HDAC inhibitors decreased the level of e2f-dependent
transcription, with the concominant reduction of mRNA level of e2f1 gene. HDAC inhibitors also affected the
survival of MESC. A 2 day TSA treatment resulted in massive detachment and cell death, as confirmed by DNA laddering
and MTT assay. Treatment with TSA for 2 and 5 days did not induce SA-βGal, activity and p16ink4a transcription,
i. e. characteristic features of senescent fibroblasts. In summary, HDAC inhibitors decrease the rate of
proliferation affecting cell cycle and viability of MESC. We conclude that MESC are unable to realize a sustainable
block of the cell cycle upon treatment with HDAC inhibitors.
Key words: murine embryonic stem cells, proliferation, histone deacetylase inhibitors
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